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13 pages, 1256 KiB

Open AccessArticle

Exogenous Melatonin Improves Fruit Quality Features, Health Promoting Antioxidant Compounds and Yield Traits in Tomato Fruits under Acid Rain Stress

by Biswojit Debnath, Mubasher Hussain, Min Li, Xiaocao Lu, Yueting Sun and Dongliang Qiu

Molecules 2018, 23(8), 1868; https://doi.org/10.3390/molecules23081868 - 26 Jul 2018

Cited by 48 | Viewed by 5671

Abstract

Acid rain is a serious worldwide environmental problem which reduces the growth and yield of crops. Melatonin, as a pleiotropic molecule has been known to improve stress tolerance by limiting the oxidative damage of plants exposed to adverse environments. However, the role of [...] Read more.

Acid rain is a serious worldwide environmental problem which reduces the growth and yield of crops. Melatonin, as a pleiotropic molecule has been known to improve stress tolerance by limiting the oxidative damage of plants exposed to adverse environments. However, the role of exogenous melatonin particularly on the yield and antioxidant compounds in tomato fruits under abiotic stress condition remains inexpressible. This observation aims to identify the influence of melatonin treatment under simulated acid rain (SAR) condition on fruit qualities, phenolics, flavonoids, and carotenoids concentration in fruits, and yield of tomatoes. Our study results showed that the fruits of SAR-stressed plants had higher quality traits and antioxidant bioactive compounds by increasing antioxidant activities against SAR-induced oxidative stress compared with fruits of control plants. Nonetheless, these improvements to antioxidant activities in fruits under SAR-condition remained unable to prevent the reduction of the yield. However, SAR-stressed plants treated by melatonin exhibited upgradation on the fruit quality traits, antioxidant compounds and yield attributes through accelerating oxidant-scavenging antioxidant actions in fruits compared with fruits of SAR-stressed plants. Meanwhile, our results suggest that exogenous melatonin plays an important role in improvement of bioactive compounds and yield traits in tomato fruits through regulating antioxidant system. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 2189 KiB

Open AccessArticle

Female Reproductive Performance in the Mouse: Effect of Oral Melatonin

by Xiaoxue Zhao, Dian Wang, Zhenzheng Wu, Bo Pan, Haoxuan Yang, Changjun Zeng, Ming Zhang, Guoshi Liu, Hongbing Han and Guangbin Zhou

Molecules 2018, 23(8), 1845; https://doi.org/10.3390/molecules23081845 - 25 Jul 2018

Cited by 16 | Viewed by 4043

Abstract

Although melatonin has some of the broadest ranges of actions on the physiology of vertebrates, especially on their reproductive processes, the mechanism by which melatonin regulates animal reproduction is still incompletely understood. This study was designed to determine the effect of oral melatonin [...] Read more.

Although melatonin has some of the broadest ranges of actions on the physiology of vertebrates, especially on their reproductive processes, the mechanism by which melatonin regulates animal reproduction is still incompletely understood. This study was designed to determine the effect of oral melatonin on the reproductive performance of female mice. Female ICR mice (7 weeks old) were given melatonin-containing water (3, 30 and 300 μg/mL; melatonin) or water only (control) until 10 weeks of age. Then, some of the mice were successfully mated (confirmed by vaginal plugs), and the number of live births and their weights were recorded. Some mice were used for a histological analysis of the number of follicles in the ovaries. Others were used for oocyte collection after superovulation, and in vitro fertilization (IVF) was performed. The mRNA expression of the apopotosis-related genes (BAX, BCL2) in the IVF embryos were analyzed. After melatonin administration, the mice showed similar serum melatonin levels to that of the control. The number of antral follicles per mm² unit area in the 30 μg/mL melatonin-treated group (14.60) was significantly higher than that of the control (7.78), which was lower than that of the 3 μg/mL melatonin-treated group (12.29). The litter size was significantly higher in the 3 μg/mL melatonin-treated group (15.5) than in the control (14.3). After IVF, the hatched blastocyst formation rate in the 30 μg/mL melatonin-treated group (85.70%) was significantly higher than that of the control (72.10%), and it was the same for the BCL2/BAX expression ratio. Although oral melatonin did not appear to have an effect on the serum melatonin rhythm in the mouse, melatonin did increase litter size at the 3 μg/mL dose level, and improved the developmental competency of IVF embryos at the 30 μg/mL level. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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10 pages, 2486 KiB

Open AccessArticle

Exogenous Melatonin Improves Tolerance to Water Deficit by Promoting Cuticle Formation in Tomato Plants

by Fei Ding, Gang Wang, Meiling Wang and Shuoxin Zhang

Molecules 2018, 23(7), 1605; https://doi.org/10.3390/molecules23071605 - 02 Jul 2018

Cited by 70 | Viewed by 5867

Abstract

The plant cuticle, composed of cutin and waxes, is a hydrophobic layer coating the aerial organs of terrestrial plants and playing a critical role in limiting water loss. While melatonin has been recently demonstrated to be involved in responses to drought stress in [...] Read more.

The plant cuticle, composed of cutin and waxes, is a hydrophobic layer coating the aerial organs of terrestrial plants and playing a critical role in limiting water loss. While melatonin has been recently demonstrated to be involved in responses to drought stress in plants, its relationship with cuticle formation is not known. In the present work, we report the effects of melatonin on the formation of cuticle in tomato leaves subjected to water deficit. Preliminary analysis by light microscope showed that tomato leaves pretreated with exogenous melatonin might have thicker cutin than tomato leaves without melatonin pretreatment under water deficit condition. Chemical characterization showed that exogenous application of melatonin increased the level of cuticular waxes in tomato leaves under water deficit. Consistent with the change in cuticular waxes was the increased abundance of wax-associated gene transcripts. Further, assessment of water loss and chlorophyll leaching in tomato leaves revealed the association of cuticle deposition with reduced leaf permeability, which is important in restricting water loss in water deficit-stressed tomato plants. These results suggest a role for melatonin in regulating leaf cuticle formation and non-stomatal water loss in leaves. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 2282 KiB

Open AccessArticle

Effects of Melatonin on Antioxidant Capacity in Naked Oat Seedlings under Drought Stress

by Wenying Gao, Yujing Zhang, Zheng Feng, Qingqing Bai, Jinjin He and Yingjuan Wang

Molecules 2018, 23(7), 1580; https://doi.org/10.3390/molecules23071580 - 29 Jun 2018

Cited by 91 | Viewed by 5700

Abstract

Melatonin (N-acetyl-5-methoxytryptamine, MT) is a molecule with pleiotropic effects including antioxidant activity, regulated plant growth, development, and reduced environmental stress in plants. However, only a few studies have analyzed the effect of exogenous MT on drought stress in naked oat seedlings. [...] Read more.

Melatonin (N-acetyl-5-methoxytryptamine, MT) is a molecule with pleiotropic effects including antioxidant activity, regulated plant growth, development, and reduced environmental stress in plants. However, only a few studies have analyzed the effect of exogenous MT on drought stress in naked oat seedlings. Therefore, in this study, we studied the effects of exogenous MT on the antioxidant capacity of naked oat under drought stress to understand the possible antioxidant mechanism. The results showed that a pretreatment of 100 μM MT reduced the hydrogen peroxide (H₂O₂) and superoxide anion (O²⁻•) contents. MT also enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activities in the leaves of naked oat seedlings under 20% PEG-6000 drought stress. MT upregulated the expression levels of the mitogen-activated protein kinases (MAPKs) Asmap1 and Aspk11, and the transcription factor (TF) genes (except for NAC), WRKY1, DREB2, and MYB increased in drought with MT pretreatment seedlings when compared with seedlings exposed to drought stress alone. These data indicated that the MT-mediated induction of the antioxidant response may require the activation of reactive oxygen species (ROS) and MAPK, followed by triggering a downstream MAPK cascade such as Asmap1 and Aspk11, to regulate the expression of antioxidant-related genes. This study demonstrated that MT could induce the expression of MAPKs and TFs and regulate the expression of downstream stress-responsive genes, thereby increasing the plant’s tolerance. This may provide a new idea for MT modulation in the regulation of plant antioxidant defenses. These results provide a theoretical basis for MT to alleviate drought stress in naked oat. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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16 pages, 5158 KiB

Open AccessArticle

Mitochondria Transcription Factor A: A Putative Target for the Effect of Melatonin on U87MG Malignant Glioma Cell Line

by Daiane G. Franco, Isabele F. Moretti and Suely K. N. Marie

Molecules 2018, 23(5), 1129; https://doi.org/10.3390/molecules23051129 - 09 May 2018

Cited by 33 | Viewed by 4698

Abstract

The disruption of mitochondrial activity has been associated with cancer development because it contributes to regulating apoptosis and is the main source of reactive oxygen species (ROS) production. Mitochondrial transcription factor A (TFAM) is a protein that maintains mitochondrial DNA (mtDNA) integrity, and [...] Read more.

The disruption of mitochondrial activity has been associated with cancer development because it contributes to regulating apoptosis and is the main source of reactive oxygen species (ROS) production. Mitochondrial transcription factor A (TFAM) is a protein that maintains mitochondrial DNA (mtDNA) integrity, and alterations in its expression are associated with mitochondrial damage and cancer development. In addition, studies have shown that mitochondria are a known target of melatonin, the pineal gland hormone that plays an important anti-tumorigenic role. Thus, we hypothesized that melatonin decreases the expression of TFAM (RNA and protein) in the human glioblastoma cell line U87MG, which disrupts mtDNA expression and results in cell death due to increased ROS production and mitochondrial damage. Our results confirm the hypothesis, and also show that melatonin reduced the expression of other mitochondrial transcription factors mRNA (TFB1M and TFB2M) and interfered with mtDNA transcription. Moreover, melatonin delayed cell cycle progression and potentiated the reduction of cell survival due to treatment with the chemotherapeutic agent temozolomide. In conclusion, elucidating the effect of melatonin on TFAM expression should help to understand the signaling pathways involved in glioblastoma progression, and melatonin could be potentially applied in the treatment of this type of brain tumor. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 1421 KiB

Open AccessArticle

Cold Priming Induced Tolerance to Subsequent Low Temperature Stress is Enhanced by Melatonin Application during Recovery in Wheat

by Luying Sun, Xiangnan Li, Zongshuai Wang, Zhongwei Sun, Xiancan Zhu, Shengqun Liu, Fengbin Song, Fulai Liu and Yongjun Wang

Molecules 2018, 23(5), 1091; https://doi.org/10.3390/molecules23051091 - 04 May 2018

Cited by 57 | Viewed by 5091

Abstract

Cold priming can alleviate the effects of subsequent cold stress on wheat plant growth. Melatonin plays a key role in cold stress response in plants. In this study, the effects of foliar melatonin application during recovery on the cold tolerance of cold primed [...] Read more.

Cold priming can alleviate the effects of subsequent cold stress on wheat plant growth. Melatonin plays a key role in cold stress response in plants. In this study, the effects of foliar melatonin application during recovery on the cold tolerance of cold primed wheat plants were investigated. It was found that both melatonin and cold priming increased the photosynthetic rate and stomatal conductance, enhanced the activities of antioxidant enzymes, and altered the related gene expressions in wheat under cold stress. Melatonin application is helpful for the photosynthetic carbon assimilation and membrane stability of the cold primed plants under cold stress. These results suggested that foliar melatonin application during recovery enhanced the cold priming induced tolerance to subsequent low temperature stress in wheat. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 1610 KiB

Open AccessArticle

The Tryptophan Decarboxylase in Solanum lycopersicum

by Xin Pang, Yanping Wei, Yuan Cheng, Luzhao Pan, Qingjing Ye, Rongqing Wang, Meiying Ruan, Guozhi Zhou, Zhuping Yao, Zhimiao Li, Yuejian Yang, Weicheng Liu and Hongjian Wan

Molecules 2018, 23(5), 998; https://doi.org/10.3390/molecules23050998 - 24 Apr 2018

Cited by 20 | Viewed by 4401

Abstract

Melatonin plays an important role in plant growth, development, and environmental stress. In this study, a systematic analysis of tomato tryptophan decarboxylase (SlTrpDC), which is the first enzyme of melatonin biosynthesis, was conducted by integrating structural features, phylogenetic relationships, an exon/intron feature, and [...] Read more.

Melatonin plays an important role in plant growth, development, and environmental stress. In this study, a systematic analysis of tomato tryptophan decarboxylase (SlTrpDC), which is the first enzyme of melatonin biosynthesis, was conducted by integrating structural features, phylogenetic relationships, an exon/intron feature, and a divergent expression profile. The results determined that the tomato genome encoded five members (SlTrpDC1-SlTrpDC5). The phylogenetic relationships indicated that gene expansion was proposed as the major mode of evolution of the TrpDC genes from the different plant algae species to the higher plants species. The analyses of the exon/intron configurations revealed that the intron loss events occurred during the structural evolution of the TrpDCs in plants. Additionally, the RNA-seq and qRT-PCR analysis revealed that the expression of the SlTrpDC3 was high in all of the tested tissues, while the SlTrpDC4 and SlTrpDC5 were not expressed. The expression patterns of the remaining two (SlTrpDC1 and SlTrpDC2) were tissue-specific, which indicated that these genes may play important roles within the different tissues. No expression difference was observed in the tomato plants in response to the biotic stresses. This study will expand the current knowledge of the roles of the TrpDC genes in tomato growth and development. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 721 KiB

Open AccessArticle

Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post-Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring

by You-Lin Tain, Steve Leu, Wei-Chia Lee, Kay L. H. Wu and Julie Y. H. Chan

Molecules 2018, 23(4), 886; https://doi.org/10.3390/molecules23040886 - 11 Apr 2018

Cited by 16 | Viewed by 3687

Abstract

Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced [...] Read more.

Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced programmed hypertension in adult offspring. Pregnant Sprague-Dawley rats received either a normal diet (ND) or a 60% fructose diet (HF) during pregnancy and the lactation period. Male offspring were on either the ND or a high-salt diet (HS, 1% NaCl) from weaning to 12 weeks of age and were assigned to five groups (n = 8/group): ND/ND, HF/ND, ND/HS, HF/HS, and HF/HS+melatonin. Melatonin (0.01% in drinking water) was administered during pregnancy and lactation. We observed that maternal HF combined with post-weaning HS diets induced hypertension in male adult offspring, which was attenuated by maternal melatonin therapy. The beneficial effects of maternal melatonin therapy on HF/HS-induced hypertension related to regulating several nutrient-sensing signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a. Additionally, melatonin increased protein levels of mammalian targets of rapamycin (mTOR), decreased plasma asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine levels, and increased the l-arginine-to-ADMA ratio. The reprogramming effects by which maternal melatonin therapy protects against hypertension of developmental origin awaits further elucidation. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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18 pages, 8054 KiB

Open AccessArticle

Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings

by Jun Ni, Qiaojian Wang, Faheem Afzal Shah, Wenbo Liu, Dongdong Wang, Shengwei Huang, Songling Fu and Lifang Wu

Molecules 2018, 23(4), 799; https://doi.org/10.3390/molecules23040799 - 30 Mar 2018

Cited by 131 | Viewed by 7757

Abstract

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the [...] Read more.

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 30897 KiB

Open AccessArticle

Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic Injury in Experimental Burns

by Minka Hristova, Maria Tzaneva, Ganka Bekyarova, Dariya Chivchibashi, Nadezhda Stefanova and Yoana Kiselova-Kaneva

Molecules 2018, 23(4), 749; https://doi.org/10.3390/molecules23040749 - 24 Mar 2018

Cited by 6 | Viewed by 4442

Abstract

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in [...] Read more.

Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94–1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06–1.23), p < 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios (p < 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98–1.61) and 1.16 (1.01–1.25), p < 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74–0.96), p < 0.01) and upregulated Nrf2 (1.55 (1.52–1.65), p < 0.001) levels. It also augmented Bax (1.68 (1.5–1.8), p < 0.001) and Bcl-2 expressions (1.96 (1.89–2.01), p < 0.0001), but reduced Bax/Bcl-2 ratios (p < 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax/Bcl-2 ratio modification as well. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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15 pages, 22251 KiB

Open AccessArticle

The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study

by Jin-Young Sung, Ji-Hyun Bae, Jong-Ha Lee, Yoon-Nyun Kim and Dae-Kwang Kim

Molecules 2018, 23(4), 737; https://doi.org/10.3390/molecules23040737 - 23 Mar 2018

Cited by 18 | Viewed by 7307

Abstract

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and [...] Read more.

The activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) via phosphorylation in the hippocampus is an important signaling mechanism for enhancing memory processing. Although melatonin is known to increase CREB expression in various animal models, the signaling mechanism between melatonin and CREB has been unknown in vitro. Thus, we confirmed the signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated with long-term memory processing through phosphorylation of Raf, ERK, p90RSK, CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT pathways were not involved in this signaling pathway by melatonin in HT-22 cells. Furthermore, we investigated whether melatonin regulated the expressions of CREB-BDNF associated with long-term memory processing in aged HT-22 cells. In conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in the in vitro long-term memory processing model and increased the levels of p-CREB and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells in the cellular aged state. Therefore, this paper suggests that melatonin induces CREB signaling pathways associated with long-term memory processing in vitro. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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12 pages, 1244 KiB

Open AccessArticle

Association of Melatonin Production with Seasonal Changes, Low Temperature, and Immuno-Responses in Hamsters

by Xiaoying Xu, Xiaoyan Liu, Shuran Ma, Ya Xu, Ying Xu, Xiazhen Guo and Dekui Li

Molecules 2018, 23(3), 703; https://doi.org/10.3390/molecules23030703 - 20 Mar 2018

Cited by 12 | Viewed by 4720

Abstract

Seasonal changes impact the melatonin production and immuno-activities in vertebrates. This is believed due to the photoperiodic alterations of the different seasons which impact the functions of pineal gland. The short photoperiod promotes pineal melatonin production. As a result, during the winter, animals [...] Read more.

Seasonal changes impact the melatonin production and immuno-activities in vertebrates. This is believed due to the photoperiodic alterations of the different seasons which impact the functions of pineal gland. The short photoperiod promotes pineal melatonin production. As a result, during the winter, animals have significantly higher levels of melatonin than in summer. However, the seasonal changes also include temperature changes. This factor has never been systemically investigated in animals. In the current study, we observed that increased temperature had limited influence on melatonin production. In contrast, cold temperature is the major factor to induce melatonin production in hamsters. Cold temperature per se can upregulate the expressions of melatonin synthetic gene AANAT and ASMT, which are the important enzymes for melatonin biosynthesis. The elevated melatonin levels induced by the cold exposure in hamster in turn, improve the immuno-responses of the animals with increased levels of IL1, 6, and 10 as well CD3. In addition, melatonin as a potent antioxidant and thermogenic agent would improve the survival chance of animals during cold weather. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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20 pages, 6455 KiB

Open AccessArticle

Melatonin Balance the Autophagy and Apoptosis by Regulating UCP2 in the LPS-Induced Cardiomyopathy

by Pan Pan, Hongmin Zhang, Longxiang Su, Xiaoting Wang and Dawei Liu

Molecules 2018, 23(3), 675; https://doi.org/10.3390/molecules23030675 - 16 Mar 2018

Cited by 67 | Viewed by 6573

Abstract

To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including [...] Read more.

To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca²⁺ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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11 pages, 6073 KiB

Open AccessArticle

Melatonin Improves Heat Tolerance in Kiwifruit Seedlings through Promoting Antioxidant Enzymatic Activity and Glutathione S-Transferase Transcription

by Dong Liang, Fan Gao, Zhiyou Ni, Lijin Lin, Qunxian Deng, Yi Tang, Xun Wang, Xian Luo and Hui Xia

Molecules 2018, 23(3), 584; https://doi.org/10.3390/molecules23030584 - 06 Mar 2018

Cited by 90 | Viewed by 6364

Abstract

Evidence exists to suggest that melatonin (MT) is important to abiotic stress tolerance in plants. Here, we investigated whether exogenous MT reduces heat damage on biological parameters and gene expression in kiwifruit (Actinidia deliciosa) seedlings. Pretreatment with MT alleviates heat-induced oxidative [...] Read more.

Evidence exists to suggest that melatonin (MT) is important to abiotic stress tolerance in plants. Here, we investigated whether exogenous MT reduces heat damage on biological parameters and gene expression in kiwifruit (Actinidia deliciosa) seedlings. Pretreatment with MT alleviates heat-induced oxidative harm through reducing H₂O₂ content and increasing proline content. Moreover, MT application raised ascorbic acid (AsA) levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). We also observed elevation in the activity of enzymes related to the AsA-GSH cycle, such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR). Furthermore, MT application increased the expression of 28/31 glutathione S-transferase (GST) genes, reducing oxidative stress. These results clearly indicate that in kiwifruit, MT exerts a protective effect against heat-related damage through regulating antioxidant pathways. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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20 pages, 4574 KiB

Open AccessArticle

Tolerance to Stress Combination in Tomato Plants: New Insights in the Protective Role of Melatonin

by Vicente Martinez, Manuel Nieves-Cordones, Maria Lopez-Delacalle, Reyes Rodenas, Teresa C. Mestre, Francisco Garcia-Sanchez, Francisco Rubio, Pedro A. Nortes, Ron Mittler and Rosa M. Rivero

Molecules 2018, 23(3), 535; https://doi.org/10.3390/molecules23030535 - 28 Feb 2018

Cited by 251 | Viewed by 14698

Abstract

Abiotic stresses such as drought, heat or salinity are major causes of yield loss worldwide. Recent studies have revealed that the acclimation of plants to a combination of different environmental stresses is unique and therefore cannot be directly deduced from studying the response [...] Read more.

Abiotic stresses such as drought, heat or salinity are major causes of yield loss worldwide. Recent studies have revealed that the acclimation of plants to a combination of different environmental stresses is unique and therefore cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. The efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Here, we report on the role of melatonin in the protection of the photosynthetic apparatus through the increase in ROS detoxification in tomato plants grown under the combination of salinity and heat, two of the most common abiotic stresses known to act jointly. Plants treated with exogenous melatonin showed a different modulation in the expression on some antioxidant-related genes and their related enzymes. More specifically, ascorbate peroxidase, glutathione reductase, glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase (APX, GR, GPX and Ph-GPX, resepctively) showed an antagonistic regulation as compared to plants that did not receive melatonin. This translated into a better antioxidant capacity and to a lesser ROS accumulation under stress combination. The performance of the photosynthesis parameters and the photosystems was also increased in plants treated with exogenous melatonin under the combination of salinity and heat. In accordance with these findings, tomato plants treated with melatonin were found to grow better under stress combination that the non-treated ones. Our study highlights the important role that exogenous melatonin plays in the acclimation of plants to a combination of two different abiotic stresses, and how this compound can specifically regulate oxidative stress-related genes and enzymes to increase plant tolerance. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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17 pages, 3395 KiB

Open AccessArticle

Melatonin in Apples and Juice: Inhibition of Browning and Microorganism Growth in Apple Juice

by Haixia Zhang, Xuan Liu, Ting Chen, Yazhen Ji, Kun Shi, Lin Wang, Xiaodong Zheng and Jin Kong

Molecules 2018, 23(3), 521; https://doi.org/10.3390/molecules23030521 - 27 Feb 2018

Cited by 31 | Viewed by 6622

Abstract

Synthetic melatonin (N-acetyl-5-methoxytryptamine, MT) is popular in the US and Asian markets as a health supplement. Here, we identified a naturally occurring melatonin source in apple juice. Melatonin was present in all 18 apple cultivars tested. The highest melatonin level of [...] Read more.

Synthetic melatonin (N-acetyl-5-methoxytryptamine, MT) is popular in the US and Asian markets as a health supplement. Here, we identified a naturally occurring melatonin source in apple juice. Melatonin was present in all 18 apple cultivars tested. The highest melatonin level of the edible part of apple was detected in the apple peel. The melatonin content in ‘Fuji’ apple juice is comparable to the level of its flesh. Melatonin was consumed during the process of juicing due to its interaction with the oxidants. Melatonin addition significantly reduced the juice color change to brown (browning). The mechanism is that melatonin scavenges the free radicals, which was indicated by the ASBT analysis; therefore, inhibiting the conversion of o-diphenolic compounds into quinones. Most importantly, melatonin exhibited powerful anti-microorganism activity in juice. The exact mechanisms of this action are currently unknown. These effects of melatonin can preserve the quality and prolong the shelf life of apple juice. The results provide valuable information regarding commerciall apple juice processing and storage. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 3201 KiB

Open AccessArticle

Melatonin-Mediated Development of Ovine Cumulus Cells, Perhaps by Regulation of DNA Methylation

by Yi Fang, Shoulong Deng, Jinlong Zhang, Haijun Liu, Yihai Li, Xiaosheng Zhang and Yixun Liu

Molecules 2018, 23(2), 494; https://doi.org/10.3390/molecules23020494 - 23 Feb 2018

Cited by 16 | Viewed by 4610

Abstract

Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) [...] Read more.

Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to age-specific epigenetic events. This study was designed to determine effects of melatonin treatment of donors on methylation modification of pre-pubertal cumulus cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs) were collected from eighteen lambs which were randomly divided into control group (C) and melatonin group given an 18 mg melatonin implant subcutaneous (M). Compared to the C group, the M group had higher concentrations of melatonin in plasma and follicular fluid (p < 0.05), greater superovulation, a higher proportion of fully expanded COCs, and a lower proportion of apoptotic cumulus cells (p < 0.05). Real-time PCR results showed that melatonin up-regulated expression of genes MT1, Bcl2, DNMT1, DNMT3a and DNMT3b, but down-regulated expression of genes p53, Caspase 3 and Bax (p < 0.05). Furthermore, melatonin increased FI of FITC (global methylation level) on cumulus cells (p < 0.05). To understand the regulation mechanism, the DNMTs promoter methylation sequence were analyzed. Compared to the C group, although there was less methylation at two CpG sites of DNMT1 (p < 0.05) and higher methylation at two CpG sites of DNMT3a (p < 0.05), there were no significant differences in methylation of the detected DNMT1 and DNMT3a promoter regions. However, there were lower methylation levels at five CpG sites of DNMT3b, which decreased methylation of detected DNMT3b promoter region on M group (p < 0.05). In conclusion, alterations of methylation regulated by melatonin may mediate development of cumulus cells in lambs. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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15 pages, 4517 KiB

Open AccessArticle

Exogenous Melatonin Mitigates Acid Rain Stress to Tomato Plants through Modulation of Leaf Ultrastructure, Photosynthesis and Antioxidant Potential

by Biswojit Debnath, Mubasher Hussain, Muhammad Irshad, Sangeeta Mitra, Min Li, Shuang Liu and Dongliang Qiu

Molecules 2018, 23(2), 388; https://doi.org/10.3390/molecules23020388 - 11 Feb 2018

Cited by 81 | Viewed by 7808

Abstract

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain [...] Read more.

Acid rain (AR) is a serious global environmental issue causing physio-morphological changes in plants. Melatonin, as an indoleamine molecule, has been known to mediate many physiological processes in plants under different kinds of environmental stress. However, the role of melatonin in acid rain stress tolerance remains inexpressible. This study investigated the possible role of melatonin on different physiological responses involving reactive oxygen species (ROS) metabolism in tomato plants under simulated acid rain (SAR) stress. SAR stress caused the inhibition of growth, damaged the grana lamella of the chloroplast, photosynthesis, and increased accumulation of ROS and lipid peroxidation in tomato plants. To cope the detrimental effect of SAR stress, plants under SAR condition had increased both enzymatic and nonenzymatic antioxidant substances compared with control plants. But such an increase in the antioxidant activities were incapable of inhibiting the destructive effect of SAR stress. Meanwhile, melatonin treatment increased SAR-stress tolerance by repairing the grana lamella of the chloroplast, improving photosynthesis and antioxidant activities compared with those in SAR-stressed plants. However, these possible effects of melatonin are dependent on concentration. Moreover, our study suggests that 100-μM melatonin treatment improved the SAR-stress tolerance by increasing photosynthesis and ROS scavenging antioxidant activities in tomato plants. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 3338 KiB

Open AccessArticle

Melatonin Alleviates High Temperature-Induced Pollen Abortion in Solanum lycopersicum

by Zhen-Yu Qi, Kai-Xin Wang, Meng-Yu Yan, Mukesh Kumar Kanwar, Dao-Yi Li, Leonard Wijaya, Mohammed Nasser Alyemeni, Parvaiz Ahmad and Jie Zhou

Molecules 2018, 23(2), 386; https://doi.org/10.3390/molecules23020386 - 11 Feb 2018

Cited by 82 | Viewed by 6108

Abstract

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation [...] Read more.

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation treatment with melatonin (20 µM) effectively ameliorated high temperature-induced inactivation of pollen and inhibition of pollen germination in tomato (Solanum lycopersicum) plants. Melatonin alleviated reactive oxygen species production in tomato anthers under high temperature by the up-regulation of the transcription and activities of several antioxidant enzymes. Transmission electron micrograph results showed that high temperature-induced pollen abortion is associated with a premature degeneration of the tapetum cells and the formation of defective pollen grains with degenerated nuclei at the early uninuclear microspore stage, whilst melatonin protected degradation of organelles by enhancing the expression of heat shock protein genes to refold unfolded proteins and the expression of autophagy-related genes and formation of autophagosomes to degrade denatured proteins. These findings suggest a novel function of melatonin to protect pollen activity under high temperature and support the potential effects of melatonin on reproductive development of plants. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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12 pages, 1862 KiB

Open AccessArticle

Evaluation of Melatonin Secretion and Metabolism Exponents in Patients with Ulcerative and Lymphocytic Colitis

by Cezary Chojnacki, Janusz Błasiak, Jakub Fichna, Jan Chojnacki and Tomasz Popławski

Molecules 2018, 23(2), 272; https://doi.org/10.3390/molecules23020272 - 29 Jan 2018

Cited by 14 | Viewed by 4173

Abstract

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of [...] Read more.

Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C—13.4 ± 4.8 µg/24 h, group UC—7.8 ± 2.6 µg/24 h (p < 0.01), group LC—19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s—in patients with UC − r = −0.888 and with LC − r = −0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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15 pages, 3181 KiB

Open AccessArticle

Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in l-NAME-Induced Hypertension

by Fedor Simko, Tomas Baka, Kristina Krajcirovicova, Kristina Repova, Silvia Aziriova, Stefan Zorad, Marko Poglitsch, Michaela Adamcova, Russel J. Reiter and Ludovit Paulis

Molecules 2018, 23(2), 265; https://doi.org/10.3390/molecules23020265 - 29 Jan 2018

Cited by 41 | Viewed by 7244

Abstract

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the [...] Read more.

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old male Wistar rats (n = 10) were treated as follows for four weeks: untreated controls, rats treated with melatonin (10 mg/kg/day), rats treated with l-NAME (40 mg/kg/day), and rats treated with l-NAME + melatonin. l-NAME administration led to hypertension and left ventricular (LV) fibrosis in terms of enhancement of soluble, insoluble and total collagen concentration and content. Melatonin reduced systolic blood pressure enhancement and lowered the concentration and content of insoluble and total collagen in the LV. The serum concentration of angiotensin (Ang) 1–8 (Ang II) and its downstream metabolites were reduced in the l-NAME group and remained unaltered by melatonin. The serum aldosterone level and its ratio to Ang II (AA2-ratio) were increased in the l-NAME group without being modified by melatonin. We conclude that l-NAME-hypertension is associated with reduced level of Ang II and its downstream metabolites and increased aldosterone concentration and AA2-ratio. Melatonin exerts its protective effect in l-NAME-induced hypertension without affecting RAAS. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 3754 KiB

Open AccessArticle

Exogenous Melatonin Alleviates Cold Stress by Promoting Antioxidant Defense and Redox Homeostasis in Camellia sinensis L.

by Xin Li, Ji-Peng Wei, Eric R. Scott, Jian-Wei Liu, Shuai Guo, Yang Li, Lan Zhang and Wen-Yan Han

Molecules 2018, 23(1), 165; https://doi.org/10.3390/molecules23010165 - 15 Jan 2018

Cited by 142 | Viewed by 7485

Abstract

The unprecedented early spring frost that appears as a cold stress adversely affects growth and productivity in tea (Camellia sinensis L.); therefore, it is indispensable to develop approaches to improve the cold tolerance of tea. Here, we investigated the effect of pretreatment [...] Read more.

The unprecedented early spring frost that appears as a cold stress adversely affects growth and productivity in tea (Camellia sinensis L.); therefore, it is indispensable to develop approaches to improve the cold tolerance of tea. Here, we investigated the effect of pretreatment with exogenous melatonin on the net photosynthetic rate, the maximum photochemical efficiency of PSII, chlorophyll content, lipid peroxidation, reactive oxygen species (ROS) accumulation, antioxidant potential, and redox homeostasis in leaves of tea plants following cold stress. Our results revealed that cold treatment induced oxidative stress by increasing ROS accumulation, which in turn affected the photosynthetic process in tea leaves. However, treatment with melatonin mitigated cold-induced reductions in photosynthetic capacity by reducing oxidative stress through enhanced antioxidant potential and redox homeostasis. This study provides strong evidence that melatonin could alleviate cold-induced adverse effects in tea plants. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessFeature PaperArticle

Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates

by Silvia Carloni, Fabrizio Proietti, Marco Rocchi, Mariangela Longini, Lucia Marseglia, Gabriella D’Angelo, Walter Balduini, Eloisa Gitto and Giuseppe Buonocore

Molecules 2017, 22(12), 2115; https://doi.org/10.3390/molecules22122115 - 01 Dec 2017

Cited by 58 | Viewed by 9625

Abstract

Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was [...] Read more.

Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24–72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg⁻¹ melatonin, or 3 boluses of 1 or 5 mg·kg⁻¹ of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC) from 10.48 to 118.17 µg·mL⁻¹·h⁻¹. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results

by Minghui Yang, Jingli Tao, Menglong Chai, Hao Wu, Jing Wang, Guangdong Li, Changjiu He, Lu Xie, Pengyun Ji, Yunping Dai, Liguo Yang and Guoshi Liu

Molecules 2017, 22(12), 2059; https://doi.org/10.3390/molecules22122059 - 27 Nov 2017

Cited by 51 | Viewed by 8750

Abstract

The inferior oocytes (IOs), which are not suitable for embryo development, occupy roughly one-third or more of the collected immature bovine oocytes. The IOs are usually discarded from the in vitro bovine embryo production process. Improving the quality of the inferior oocytes (IOs) [...] Read more.

The inferior oocytes (IOs), which are not suitable for embryo development, occupy roughly one-third or more of the collected immature bovine oocytes. The IOs are usually discarded from the in vitro bovine embryo production process. Improving the quality of the inferior oocytes (IOs) and make them available in in vitro embryo production would have important biological, as well as commercial, value. This study was designed to investigate whether melatonin could improve the quality of IOs and make them usable in the in vitro maturation (IVM) and subsequent (in vitro fertilization) IVF embryo development. The results indicated that: the maturation rate of IOs and their subsequent IVF embryo developments were impaired compared to cumulus-oocyte complexes and melatonin treatment significantly improved the quality of IOs, as well as their IVF and embryo developments. The potential mechanisms are that: (1) melatonin reduced reactive oxygen species (ROS) and enhanced glutathione (GSH) levels in the IOs, thereby protecting them from oxidative stress; (2) melatonin improved mitochondrial normal distribution and function to increase ATP level in IOs; and (3) melatonin upregulated the expression of ATPase 6, BMP-15, GDF-9, SOD-1, Gpx-4, and Bcl-2, which are critical genes for oocyte maturation and embryo development and downregulated apoptotic gene expression of caspase-3. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

Genomic Analysis of the ASMT Gene Family in Solanum lycopersicum

by Weicheng Liu, Dake Zhao, Chunfang Zheng, Chen Chen, Xin Peng, Yuan Cheng and Hongjian Wan

Molecules 2017, 22(11), 1984; https://doi.org/10.3390/molecules22111984 - 16 Nov 2017

Cited by 27 | Viewed by 4786

Abstract

Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the [...] Read more.

Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the integration of the structural features, phylogenetic relationships, exon/intron configuration, and expression profile during growth and development, as well as biotic stresses. The results revealed that the tomato genome encoded a minimum of 14 members, containing three probable encoded pseudogenes. Chromosome mapping indicated that the family had probably expanded via tandem duplication events. Genome-wide RNA-seq and qRT-PCR based gene expression analysis revealed that almost half of the SlASMT genes were expressed in at least one of the experimental stages studied and also showed differential accumulation. Furthermore, the tandem duplicated SlASMT genes showed differential expression levels, which indicated probable functional divergence during the course of the evolution. Finally, this study also determined that some SlASMT genes were induced by multiple pathogens. The results suggested that these genes could be involved in tomato plant response to biotic stresses. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

Endotoxin-Induced Inflammation Suppresses the Effect of Melatonin on the Release of LH from the Ovine Pars Tuberalis Explants—Ex Vivo Study

by Karolina Wojtulewicz, Dorota Tomaszewska-Zaremba and Andrzej Przemysław Herman

Molecules 2017, 22(11), 1933; https://doi.org/10.3390/molecules22111933 - 10 Nov 2017

Cited by 9 | Viewed by 3432

Abstract

The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found [...] Read more.

The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found that the secretory activity of the pituitary may be dependent on the immune status of the animal. Therefore, this study was designed to determine the role of melatonin in the modulation of luteinizing hormone (LH) secretion from the PT explants collected from saline- and endotoxin-treated ewes in the follicular phase of the oestrous cycle. Twelve Blackhead ewes were sacrificed 3 h after injection with lipopolysaccharide (LPS; 400 ng/kg) or saline, and the PTs were collected. Each PT was cut into 4 explants, which were then divided into 4 groups: I, incubated with ‘pure’ medium 199; II, treated with gonadotropin-releasing hormone (GnRH) (100 pg/mL); III, treated with melatonin (10 nmol/mL); and IV, incubated with GnRH and melatonin. Melatonin reduced (p < 0.05) GnRH-induced secretion of LH only in the PT from saline-treated ewes. Explants collected from LPS-treated ewes were characterized by lower (p < 0.05) GnRH-dependent response in LH release. It was also found that inflammation reduced the gene expression of the GnRH receptor and the MT1 melatonin receptors in the PT. Therefore, it was shown that inflammation affects the melatonin action on LH secretion from the PT, which may be one of the mechanisms via which immune/inflammatory challenges disturb reproduction processes in animals. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

The Regulatory Mechanism of MLT/MT1 Signaling on the Growth of Antler Mesenchymal Cells

by Feifei Yang, Changjiu He, Xuyang Sun, Jing Wang, Can Luo, Guoshi Liu, Liguo Yang, Jiajun Xiong and Lijun Huo

Molecules 2017, 22(10), 1793; https://doi.org/10.3390/molecules22101793 - 23 Oct 2017

Cited by 9 | Viewed by 5415

Abstract

Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of [...] Read more.

Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further elucidated. In this work, we detected the effects of MLT/MT1 signaling on mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1-R signaling. The results show that (1) deer antler mesenchymal cells actually express MT1; (2) exogenous melatonin significantly promotes mesenchymal cells proliferation, while MT1 knock-down significantly impairs the positive effects of melatonin; and (3) melatonin significantly enhanced IGF1/IGF1-R signaling, as both the expression of IGF1 and IGF-1R increased, while MT1 knock-down significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal proliferation, which may be mediated by IGF1/IGF1-R. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessCommunication

Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants

by Hyoung-Yool Lee and Kyoungwhan Back

Molecules 2017, 22(10), 1791; https://doi.org/10.3390/molecules22101791 - 23 Oct 2017

Cited by 38 | Viewed by 5371

Abstract

Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl₂ or AlCl [...] Read more.

Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl₂ or AlCl₃ and monitored the structures of subcellular organelles—such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER)—using confocal microscopic analysis. Unlike AlCl₃ treatment, CdCl₂ (0.5 mM) treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT) to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress

by Zhiyu Zuo, Luying Sun, Tianyu Wang, Peng Miao, Xiancan Zhu, Shengqun Liu, Fengbin Song, Hanping Mao and Xiangnan Li

Molecules 2017, 22(10), 1727; https://doi.org/10.3390/molecules22101727 - 18 Oct 2017

Cited by 63 | Viewed by 6095

Abstract

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed [...] Read more.

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children

by Mariam Chahbouni, María Del Señor López, Antonio Molina-Carballo, Tomás De Haro, Antonio Muñoz-Hoyos, Marisol Fernández-Ortiz, Ana Guerra-Librero and Darío Acuña-Castroviejo

Molecules 2017, 22(10), 1728; https://doi.org/10.3390/molecules22101728 - 14 Oct 2017

Cited by 24 | Viewed by 6855

Abstract

Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic [...] Read more.

Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8–10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessArticle

A Comparative Genomic and Transcriptomic Survey Provides Novel Insights into N-Acetylserotonin Methyltransferase (ASMT) in Fish

by Kai Zhang, Zhiqiang Ruan, Jia Li, Chao Bian, Xinxin You, Steven L. Coon and Qiong Shi

Molecules 2017, 22(10), 1653; https://doi.org/10.3390/molecules22101653 - 02 Oct 2017

Cited by 11 | Viewed by 4842

Abstract

Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic [...] Read more.

Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic survey to explore the ASMT family in fish. Two ASMT isotypes (ASMT1 and ASMT2) and a new ASMT-like (ASMTL) are all extracted from teleost genomes on the basis of phylogenetic and synteny analyses. We confirmed that C-terminal of the ASMTL proteins (ASMTL-ASMT) is homology to the full length of ASMT1 and ASMT2. Our results also demonstrate that the two ASMT isotypes and their distribution in teleosts seem to be the result of combinations of whole-genome duplication (WGD) and gene loss. Differences were also observed in tissue distribution and relative transcript abundances of ASMT1, ASMT2 and ASMTL through transcriptomic analysis. Protein sequence alignment and 3D structure prediction of ASMTs and ASMTL suggest differential roles for these ASMT genes. In summary, our current work provides novel insights into the ASMT genes in fish by combination of genomic and transcriptomic data. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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6449 KiB

Open AccessArticle

Exogenous Melatonin Alleviates Alkaline Stress in Malus hupehensis Rehd. by Regulating the Biosynthesis of Polyamines

by Xiaoqing Gong, Shuting Shi, Fangfang Dou, Yi Song and Fengwang Ma

Molecules 2017, 22(9), 1542; https://doi.org/10.3390/molecules22091542 - 13 Sep 2017

Cited by 83 | Viewed by 6213

Abstract

Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, [...] Read more.

Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, we examine the role of melatonin treatment in the response of Malus hupehensis Rehd. to alkaline conditions. Stressed seedlings showed chlorosis and suppressed growth. However, this phenotype was ameliorated when 5 µM melatonin was added to the irrigation solution. This supplementation was also associated with a reduction in cell membrane damage and maintenance of a normal root system architecture. Fewer reactive oxygen species (ROS) were accumulated due to the enhanced scavenging activity of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, alkaline-stressed seedlings that received the melatonin supplement accumulated more polyamines compared with untreated seedlings. Transcript levels of six genes involved in polyamine synthesis, including SAMDC1, -3, and -4, and SPDS1, -3, and -5, -6, were upregulated in response to melatonin application. All of these results demonstrate that melatonin has a positive function in plant tolerance to alkaline stress because it regulates enzyme activity and the biosynthesis of polyamines. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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763 KiB

Open AccessArticle

Effects of Sleep Quality on Melatonin Levels and Inflammatory Response after Major Abdominal Surgery in an Intensive Care Unit

by Necdet Fatih Yaşar, Bartu Badak, Ağgül Canik, Sema Şanal Baş, Sema Uslu, Setenay Öner and Ersin Ateş

Molecules 2017, 22(9), 1537; https://doi.org/10.3390/molecules22091537 - 12 Sep 2017

Cited by 12 | Viewed by 4471

Abstract

Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery. [...] Read more.

Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery. Thus, we compared the patients, who were screened in the side-rooms where the lights were dimmed and noise levels were reduced, with the patients who received usual care. Preoperative and postoperative urine 6-sulphatoxymelatonin, serum interleukin-1 (IL-1), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were measured and data on sleep quality was collected using the Richards–Campbell Sleep Questionnaire. Postoperative CRP and IL-6 levels were greater in the control group than in the experimental group, whereas postoperative 24 h melatonin levels were greater than preoperative levels and the difference was steeper in the experimental group in concordance with sleep quality scores. Thus, the regulation of light and noise in ICUs may help the recovery after major surgeries in patients, potentially by increasing melatonin production, which has anti-inflammatory properties. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Review

Jump to: Research

20 pages, 772 KiB

Open AccessReview

Melatonin and Its Effects on Plant Systems

by Rahat Sharif, Chen Xie, Haiqiang Zhang, Marino B. Arnao, Muhammad Ali, Qasid Ali, Izhar Muhammad, Abdullah Shalmani, Muhammad Azher Nawaz, Peng Chen and Yuhong Li

Molecules 2018, 23(9), 2352; https://doi.org/10.3390/molecules23092352 - 14 Sep 2018

Cited by 162 | Viewed by 10772

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) is a nontoxic biological molecule produced in a pineal gland of animals and different tissues of plants. It is an important secondary messenger molecule, playing a vital role in coping with various abiotic and biotic stresses. Melatonin serves as [...] Read more.

Melatonin (N-acetyl-5-methoxytryptamine) is a nontoxic biological molecule produced in a pineal gland of animals and different tissues of plants. It is an important secondary messenger molecule, playing a vital role in coping with various abiotic and biotic stresses. Melatonin serves as an antioxidant in postharvest technology and enhances the postharvest life of fruits and vegetables. The application of exogenous melatonin alleviated reactive oxygen species and cell damage induced by abiotic and biotic stresses by means of repairing mitochondria. Additionally, the regulation of stress-specific genes and the activation of pathogenesis-related protein and antioxidant enzymes genes under biotic and abiotic stress makes it a more versatile molecule. Besides that, the crosstalk with other phytohormones makes inroads to utilize melatonin against non-testified stress conditions, such as viruses and nematodes. Furthermore, different strategies have been discussed to induce endogenous melatonin activity in order to sustain a plant system. Our review highlighted the diverse roles of melatonin in a plant system, which could be useful in enhancing the environmental friendly crop production and ensure food safety. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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20 pages, 435 KiB

Open AccessReview

Melatonin Uptake by Cells: An Answer to Its Relationship with Glucose?

by Juan C. Mayo, Arturo Aguado, Rafael Cernuda-Cernuda, Alejandro Álvarez-Artime, Vanesa Cepas, Isabel Quirós-González, David Hevia and Rosa M. Sáinz

Molecules 2018, 23(8), 1999; https://doi.org/10.3390/molecules23081999 - 10 Aug 2018

Cited by 29 | Viewed by 4571

Abstract

Melatonin, N-acetyl-5-methoxytryptamine, is an indole mainly synthesized from tryptophan in the pineal gland and secreted exclusively during the night in all the animals reported to date. While the pineal gland is the major source responsible for this night rise, it is not [...] Read more.

Melatonin, N-acetyl-5-methoxytryptamine, is an indole mainly synthesized from tryptophan in the pineal gland and secreted exclusively during the night in all the animals reported to date. While the pineal gland is the major source responsible for this night rise, it is not at all the exclusive production site and many other tissues and organs produce melatonin as well. Likewise, melatonin is not restricted to vertebrates, as its presence has been reported in almost all the phyla from protozoa to mammals. Melatonin displays a large set of functions including adaptation to light: dark cycles, free radical scavenging ability, antioxidant enzyme modulation, immunomodulatory actions or differentiation–proliferation regulatory effects, among others. However, in addition to those important functions, this evolutionary ‘ancient’ molecule still hides further tools with important cellular implications. The major goal of the present review is to discuss the data and experiments that have addressed the relationship between the indole and glucose. Classically, the pineal gland and a pinealectomy were associated with glucose homeostasis even before melatonin was chemically isolated. Numerous reports have provided the molecular components underlying the regulatory actions of melatonin on insulin secretion in pancreatic beta-cells, mainly involving membrane receptors MTNR1A/B, which would be partially responsible for the circadian rhythmicity of insulin in the organism. More recently, a new line of evidence has shown that glucose transporters GLUT/SLC2A are linked to melatonin uptake and its cellular internalization. Beside its binding to membrane receptors, melatonin transportation into the cytoplasm, required for its free radical scavenging abilities, still generates a great deal of debate. Thus, GLUT transporters might constitute at least one of the keys to explain the relationship between glucose and melatonin. These and other potential mechanisms responsible for such interaction are also discussed here. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

15 pages, 1641 KiB

Open AccessReview

The Role of Phyto-Melatonin and Related Metabolites in Response to Stress

by Yang Yu, Yan Lv, Yana Shi, Tao Li, Yanchun Chen, Dake Zhao and Zhiwei Zhao

Molecules 2018, 23(8), 1887; https://doi.org/10.3390/molecules23081887 - 28 Jul 2018

Cited by 91 | Viewed by 7124

Abstract

Plant hormone candidate melatonin has been widely studied in plants under various stress conditions, such as heat, cold, salt, drought, heavy metal, and pathogen attack. Under stress, melatonin usually accumulates sharply by modulating its biosynthesis and metabolic pathways. Beginning from the precursor tryptophan, [...] Read more.

Plant hormone candidate melatonin has been widely studied in plants under various stress conditions, such as heat, cold, salt, drought, heavy metal, and pathogen attack. Under stress, melatonin usually accumulates sharply by modulating its biosynthesis and metabolic pathways. Beginning from the precursor tryptophan, four consecutive enzymes mediate the biosynthesis of tryptamine or 5-hydroxytryptophan, serotonin, N-acetylserotonin or 5-methoxytryptamine, and melatonin. Then, the compound is catabolized into 2-hydroxymelatonin, cyclic-3-hydroxymelatonin, and N¹-acetyl-N²-formyl-5-methoxyknuramine through 2-oxoglutarate-dependent dioxygenase catalysis or reaction with reactive oxygen species. As an ancient and powerful antioxidant, melatonin directly scavenges ROS induced by various stress conditions. Furthermore, it confreres stress tolerance by activating the plant’s antioxidant system, alleviating photosynthesis inhibition, modulating transcription factors that are involved with stress resisting, and chelating and promoting the transport of heavy metals. Melatonin is even proven to defense against pathogen attacks for the plant by activating other stress-relevant hormones, like salicylic acid, ethylene, and jasmonic acid. Intriguingly, other precursors and metabolite molecules involved with melatonin also can increase stress tolerance for plant except for unconfirmed 5-methoxytryptamine, cyclic-3-hydroxymelatonin, and N¹-acetyl-N²-formyl-5-methoxyknuramine. Therefore, the precursors and metabolites locating at the whole biosynthesis and catabolism pathway of melatonin could contribute to plant stress resistance, thus providing a new perspective for promoting plant stress tolerance. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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18 pages, 1065 KiB

Open AccessFeature PaperReview

Melatonin in Heart Failure: A Promising Therapeutic Strategy?

by Frederic Nduhirabandi and Gerald J. Maarman

Molecules 2018, 23(7), 1819; https://doi.org/10.3390/molecules23071819 - 22 Jul 2018

Cited by 37 | Viewed by 7639

Abstract

Heart failure is a multifactorial clinical syndrome characterized by the inability of the heart to pump sufficient blood to the body. Despite recent advances in medical management, poor outcomes in patients with heart failure remain very high. This highlights a need for novel [...] Read more.

Heart failure is a multifactorial clinical syndrome characterized by the inability of the heart to pump sufficient blood to the body. Despite recent advances in medical management, poor outcomes in patients with heart failure remain very high. This highlights a need for novel paradigms for effective, preventive and curative strategies. Substantial evidence supports the importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in various cardiac pathologies and cardiometabolic disorders. Melatonin plays a crucial role in major pathological processes associated with heart failure including ischemic injury, oxidative stress, apoptosis, and cardiac remodeling. In this review, available evidence for the role of melatonin in heart failure is discussed. Current challenges and possible limitations of using melatonin in heart failure are also addressed. While few clinical studies have investigated the role of melatonin in the context of heart failure, current findings from experimental studies support the potential use of melatonin as preventive and adjunctive curative therapy in heart failure. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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14 pages, 508 KiB

Open AccessReview

The Effect of Light Exposure at Night (LAN) on Carcinogenesis via Decreased Nocturnal Melatonin Synthesis

by Aldo Giudice, Anna Crispo, Maria Grimaldi, Andrea Polo, Sabrina Bimonte, Mario Capunzo, Alfonso Amore, Giovanni D’Arena, Pellegrino Cerino, Alfredo Budillon, Gerardo Botti, Susan Costantini and Maurizio Montella

Molecules 2018, 23(6), 1308; https://doi.org/10.3390/molecules23061308 - 29 May 2018

Cited by 28 | Viewed by 5445

Abstract

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that [...] Read more.

In mammals, a master clock is located within the suprachiasmatic nucleus (SCN) of the hypothalamus, a region that receives input from the retina that is transmitted by the retinohypothalamic tract. The SCN controls the nocturnal synthesis of melatonin by the pineal gland that can influence the activity of the clock’s genes and be involved in the inhibition of cancer development. On the other hand, in the literature, some papers highlight that artificial light exposure at night (LAN)-induced circadian disruptions promote cancer. In the present review, we summarize the potential mechanisms by which LAN-evoked disruption of the nocturnal increase in melatonin synthesis counteracts its preventive action on human cancer development and progression. In detail, we discuss: (i) the Warburg effect related to tumor metabolism modification; (ii) genomic instability associated with L1 activity; and (iii) regulation of immunity, including regulatory T cell (Treg) regulation and activity. A better understanding of these processes could significantly contribute to new treatment and prevention strategies against hormone-related cancer types. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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53 pages, 3302 KiB

Open AccessReview

Seasonal Reproduction in Vertebrates: Melatonin Synthesis, Binding, and Functionality Using Tinbergen’s Four Questions

by Dax ViviD and George E. Bentley

Molecules 2018, 23(3), 652; https://doi.org/10.3390/molecules23030652 - 13 Mar 2018

Cited by 31 | Viewed by 8358

Abstract

One of the many functions of melatonin in vertebrates is seasonal reproductive timing. Longer nights in winter correspond to an extended duration of melatonin secretion. The purpose of this review is to discuss melatonin synthesis, receptor subtypes, and function in the context of [...] Read more.

One of the many functions of melatonin in vertebrates is seasonal reproductive timing. Longer nights in winter correspond to an extended duration of melatonin secretion. The purpose of this review is to discuss melatonin synthesis, receptor subtypes, and function in the context of seasonality across vertebrates. We conclude with Tinbergen’s Four Questions to create a comparative framework for future melatonin research in the context of seasonal reproduction. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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36 pages, 2194 KiB

Open AccessReview

Melatonin: A Versatile Protector against Oxidative DNA Damage

by Annia Galano, Dun-Xian Tan and Russel J. Reiter

Molecules 2018, 23(3), 530; https://doi.org/10.3390/molecules23030530 - 27 Feb 2018

Cited by 188 | Viewed by 12954

Abstract

Oxidative damage to DNA has important implications for human health and has been identified as a key factor in the onset and development of numerous diseases. Thus, it is evident that preventing DNA from oxidative damage is crucial for humans and for any [...] Read more.

Oxidative damage to DNA has important implications for human health and has been identified as a key factor in the onset and development of numerous diseases. Thus, it is evident that preventing DNA from oxidative damage is crucial for humans and for any living organism. Melatonin is an astonishingly versatile molecule in this context. It can offer both direct and indirect protection against a wide variety of damaging agents and through multiple pathways, which may (or may not) take place simultaneously. They include direct antioxidative protection, which is mediated by melatonin’s free radical scavenging activity, and also indirect ways of action. The latter include, at least: (i) inhibition of metal-induced DNA damage; (ii) protection against non-radical triggers of oxidative DNA damage; (iii) continuous protection after being metabolized; (iv) activation of antioxidative enzymes; (v) inhibition of pro-oxidative enzymes; and (vi) boosting of the DNA repair machinery. The rather unique capability of melatonin to exhibit multiple neutralizing actions against diverse threatening factors, together with its low toxicity and its ability to cross biological barriers, are all significant to its efficiency for preventing oxidative damage to DNA. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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17 pages, 1402 KiB

Open AccessReview

Melatonin and Cancer Hallmarks

by Wamidh H. Talib

Molecules 2018, 23(3), 518; https://doi.org/10.3390/molecules23030518 - 26 Feb 2018

Cited by 142 | Viewed by 16083

Abstract

Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, [...] Read more.

Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. Melatonin anticancer activity is mediated by interfering with various cancer hallmarks. This review summarizes the anticancer role of melatonin in each cancer hallmark. The studies discussed in this review should serve as a solid foundation for researchers and physicians to support basic and clinical studies on melatonin as a promising anticancer agent. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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25 pages, 3895 KiB

Open AccessReview

Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

by Russel J. Reiter, Dun Xian Tan, Sergio Rosales-Corral, Annia Galano, Xin Jia Zhou and Bing Xu

Molecules 2018, 23(2), 509; https://doi.org/10.3390/molecules23020509 - 24 Feb 2018

Cited by 261 | Viewed by 22696

Abstract

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent [...] Read more.

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the “free radical theory of aging”, including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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7 pages, 492 KiB

Open AccessReview

Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A Review

by Kun Yu, Shou-Long Deng, Tie-Cheng Sun, Yuan-Yuan Li and Yi-Xun Liu

Molecules 2018, 23(2), 447; https://doi.org/10.3390/molecules23020447 - 17 Feb 2018

Cited by 70 | Viewed by 13977

Abstract

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local [...] Read more.

Melatonin is a ubiquitous molecule and exhibits different effects in long-day and short-day breeding animals. Testosterone, the main resource of androgens in the testis, is produced by Leydig cells but regulated mainly by cytokine secreted by Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and energy metabolism and, consequently, can regulate steroidogenesis. These suggest melatonin as a key player in the regulation of steroidogenesis. However, the melatonin-induced regulation of steroid hormones may differ among species, and the literature data indicate that melatonin has important effects on steroidogenesis and male reproduction. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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21 pages, 2217 KiB

Open AccessReview

Melatonin: A Molecule for Reducing Breast Cancer Risk

by Alicia González-González, María Dolores Mediavilla and Emilio J. Sánchez-Barceló

Molecules 2018, 23(2), 336; https://doi.org/10.3390/molecules23020336 - 06 Feb 2018

Cited by 47 | Viewed by 11077

Abstract

The objective of this article is to review the basis supporting the usefulness of melatonin as an adjuvant therapy for breast cancer (BC) prevention in several groups of individuals at high risk for this disease. Melatonin, as a result of its antiestrogenic and [...] Read more.

The objective of this article is to review the basis supporting the usefulness of melatonin as an adjuvant therapy for breast cancer (BC) prevention in several groups of individuals at high risk for this disease. Melatonin, as a result of its antiestrogenic and antioxidant properties, as well as its ability to improve the efficacy and reduce the side effects of conventional antiestrogens, could safely be associated with the antiestrogenic drugs presently in use. In individuals at risk of BC due to night shift work, the light-induced inhibition of melatonin secretion, with the consequent loss of its antiestrogenic effects, would be countered by administering this neurohormone. BC risk from exposure to metalloestrogens, such as cadmium, could be treated with melatonin supplements to individuals at risk of BC due to exposure to this xenoestrogen. The BC risk related to obesity may be reduced by melatonin which decrease body fat mass, inhibits the enhanced aromatase expression in obese women, increases adiponectin secretion, counteracts the oncogenic effects of elevated concentrations of leptin; and decreases blood glucose levels and insulin resistance. Despite compelling experimental evidence of melatonin’s oncostatic actions being susceptible to lowering BC risk, there is still a paucity of clinical trials focused on this subject. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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31 pages, 2072 KiB

Open AccessReview

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland

by Dun Xian Tan, Bing Xu, Xinjia Zhou and Russel J. Reiter

Molecules 2018, 23(2), 301; https://doi.org/10.3390/molecules23020301 - 31 Jan 2018

Cited by 124 | Viewed by 45546

Abstract

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the [...] Read more.

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin’s synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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19 pages, 2469 KiB

Open AccessFeature PaperReview

The Potential of Phytomelatonin as a Nutraceutical

by Marino B. Arnao and Josefa Hernández-Ruiz

Molecules 2018, 23(1), 238; https://doi.org/10.3390/molecules23010238 - 22 Jan 2018

Cited by 58 | Viewed by 15197

Abstract

Phytomelatonin (plant melatonin) is chemically related to the amino acid tryptophan and has many diverse properties. Phytomelatonin is an interesting compound due to its outstanding actions at the cellular and physiological level, especially its protective effect in plants exposed to diverse stress situations, [...] Read more.

Phytomelatonin (plant melatonin) is chemically related to the amino acid tryptophan and has many diverse properties. Phytomelatonin is an interesting compound due to its outstanding actions at the cellular and physiological level, especially its protective effect in plants exposed to diverse stress situations, while its vegetable origin offers many opportunities because it is a natural compound. We present an overview of its origin, its action in plants in general (particularly in plant species with high levels of phytomelatonin), and its possibilities for use as a nutraceutical with particular attention paid to the beneficial effects that it may have in human health. The differences between synthetic melatonin and phytomelatonin, according to its origin and purity, are presented. Finally, the current market for phytomelatonin and its limits and potentials are discussed. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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9 pages, 1041 KiB

Open AccessReview

The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development

by Yunho Jin, Jeonghyun Choi, Jinyoung Won and Yonggeun Hong

Molecules 2018, 23(1), 198; https://doi.org/10.3390/molecules23010198 - 18 Jan 2018

Cited by 30 | Viewed by 14045

Abstract

The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is [...] Read more.

The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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Open AccessFeature PaperReview

Taxon- and Site-Specific Melatonin Catabolism

by Rüdiger Hardeland

Molecules 2017, 22(11), 2015; https://doi.org/10.3390/molecules22112015 - 21 Nov 2017

Cited by 45 | Viewed by 6905

Abstract

Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism [...] Read more.

Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism can be expected upon UV exposure, e.g., in plants and in the human skin. Additionally, melatonin is more strongly nonenzymatically degraded at sites of inflammation. Typical products are several hydroxylated derivatives of melatonin and N¹-acetyl-N²-formyl-5-methoxykynuramine (AFMK). Most of these products are also formed by enzymatic catalysis. Considerable taxon- and site-specific differences are observed in the main enzymatic routes of catabolism. Formation of 6-hydroxymelatonin by cytochrome P₄₅₀ subforms are prevailing in vertebrates, predominantly in the liver, but also in the brain. In pineal gland and non-mammalian retina, deacetylation to 5-methoxytryptamine (5-MT) plays a certain role. This pathway is quantitatively prevalent in dinoflagellates, in which 5-MT induces cyst formation and is further converted to 5-methoxyindole-3-acetic acid, an end product released to the water. In plants, the major route is catalyzed by melatonin 2-hydroxylase, whose product is tautomerized to 3-acetamidoethyl-3-hydroxy-5-methoxyindolin-2-one (AMIO), which exceeds the levels of melatonin. Formation and properties of various secondary products are discussed. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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